In continuation of studies already underway, it is proposed to study the pathogenesis of amyloidosis in man and in the mouse model of the disease, and to devise tests for the evaluation of different medications in prevention and treatment. It is our intention to isolate and purify the serum component SAA, which is an acute phase lipoprotein and is the precursor of the major AA protein in secondary amyloid fibrils. SAA, purified as the high density lipoprotein by ultracentrifugation and gel filtration is, by size and charge a heterogeneous material, whose composition and origin will be studied. Purified SAA will be used to develop a radioimmunoassay for the apolipoprotein, to study the immunosuppressive effects of SAA on lymphocyte function in vitro and to look for cellular receptors for SAA. Antibodies will be raised to SAA using hybrid cell lines, obtained by fusing myeloma cells to spleen cells from immunized animals. Employing radioimmunoassays to mouse AA, we shall continue studies of the soluble factor (SAA stimulating factor) which is derived from mononuclear cells and regulates the synthesis of SAA in the liver. This factor can be generated in vitro and is used to stimulate either liver organ cultures in vitro or the intact animal to synthesize SAA. In clinical studies, the ability of antiinflammatory agents, including colchicine and steroids, to suppress the acute SAA response, will be assessed in patients with and without amyloidosis, following the injection of etiocholanolone as a standardized inflammatory stimulus. The capacity of a simple IV dose of dimethyl sulfoxide to dissolve amyloid fibrils and increase the urinary excretion of amyloid proteins will be examined in order to try to predict which patients would benefit from prolonged therapy with this solvent.